Disrupted development from head to tail: Pervasive effects of postnatal restricted resources on neurobiological, behavioral, and morphometric outcomes

Abstract

When a maternal rat nurtures her pups, she relies on adequate resources to provide optimal care for her offspring. Accordingly, limited environmental resources may result in atypical maternal care, disrupting various developmental outcomes. In the current study, maternal Long-Evans rats were randomly assigned to either a standard resource (SR) group, provided with four cups of bedding and two paper towels for nesting material or a limited resource (LR) group, provided with a quarter of the bedding and nesting material provided for the SR group. Offspring were monitored at various developmental phases throughout the study. After weaning, pups were housed in same-sex dyads in environments with SRs for continued observations. Subsequent behavioral tests revealed a sex × resource interaction in play behavior on PND 28; specifically, LR reduced play attacks in males while LR increased play attacks in females. A sex × resource interaction was also observed in anxiety-related responses in the open field task with an increase in thigmotaxis in LR females and, in the social interaction task, females exhibited more external rears oriented away from the social target. Focusing on morphological variables, tail length measurements of LR males and females were shorter on PND 9, 16, and 21; however, differences in tail length were no longer present at PND 35. Following the behavioral assessments, animals were perfused at 56 days of age and subsequent immunohistochemical assays indicated increased glucocorticoid receptors in the lateral habenula of LR offspring and higher c-Fos immunoreactivity in the basolateral amygdala of SR offspring. Further, when tail vertebrae and tail tendons were assessed via micro-CT and hydroxyproline assays, results indicated increased trabecular separation, decreased bone volume fraction, and decreased connectivity density in bones, along with reduced collagen concentration in tendons in the LR animals. In sum, although the restricted resources only persisted for a brief duration, the effects appear to be far-reaching and pervasive in this early life stress animal model.

Effects of limited bedding and nesting on postpartum mood state in rats

“…Our results showed that LBN altered maternal nursing behaviors and resulted in smaller pup weight at P3 compared to control pups. Similarly, Kent et al 36 found that low bedding was associated with decreased pup weight at P9 and P21 suggesting LBN may employed LBN in the antenatal and postnatal period while many previous studies have used a classic postpartum LBN approach which may be why our results were only partially consistent with previous LBN studies. 38,39 Additionally, the small amount of nesting materials in addition to the lack of bedding may explain some of the differences observed as previous studies have found that reduced nesting materials alone are sufficient to induce maternal stress and anxiety.…”

“…Our results showed that LBN altered maternal nursing behaviors and resulted in smaller pup weight at P3 compared to control pups. Similarly, Kent et al 36 found that low bedding was associated with decreased pup weight at P9 and P21 suggesting LBN may result in direct weight gain effects in offspring. LBN had no effect on pup retrieval or hoarding behavior in the present study.…”

Anxiety, aggression, reward sensitivity, and forebrain dopamine receptor expression in a laboratory rat model of early‐life disadvantage

“…Five of them using the wire‐floored Limited Bedding & Nesting paradigm found more anxiety behavior in a light‐dark box in both sexes of mice (Demaestri et al., 2020), reduced anxiety in male but not female rats in EPM and open field tests (Prusator & Greenwood‐Van Meerveld, 2015), no effects on open‐arm behavior in an EPM on rats of either sex but reduced open‐field center time in males (Guadagno et al., 2018), and no effects on EPM or open‐field behavior for male or female mice (Goodwill et al., 2019; Manzano‐Nieves et al., 2018). In a study using a bedding Scarcity model similar to that used here, there was no effect on EPM behavior in male or female rats (Davis et al., 2020), but more thigmotaxis in an open field in females (Kent et al., 2022). Studies involving only males found that previous Limited Bedding & Nesting produced higher anxiety in a light‐dark box, but not in an open field (Bolton et al., 2018; Yang et al., 2015) or EPM (Wearick‐Silva et al., 2019).…”